Erythropoietic Agents and Venous Thromboembolic Events in Multiple Myeloma Patients Treated with Anthracycline Based Chemotherapy and Immunomodulators.

Background: Erythropoietic agents (EPO) have recently been implicated with higher rates of thromboembolic events (VTE) in multiple myeloma (MM) patients receiving lenalidomide (R) and dexamethasone (Knight et al. NEJM 2006). Uncontrolled erythrocytosis, a recognized risk factor for VTE, may complicate therapy with EPO, but was not evaluated as a causative factor for VTE in the above report. We sought to evaluate the putative interactions between erythrocytosis, immunomodulator therapy, EPO and VTE.

Patients and Methods: We retrospectively reviewed patients’ records from 2 studies of anthracycline-based chemotherapy with immunomodulators: pegylated liposomal doxorubicin, vincristine, dexamethasone and thalidomide (T) (study A) or lenalidomide (study B) in MM. Demographic variables, aspirin therapy, EPO therapy, immunomodulator therapy (T vs R), as well as laboratory variables (which included all hemoglobin values while on study) were reviewed.

Results: From August 2001 to December 2005, 184 multiple myeloma patients with active disease were treated on study A (105) and B (79). The median age for patients was 63 and 62 years on study A and B respectively. Aspirin prophylaxis (81mg daily) was administered for all patients on study B and for all but 19 patients on study A. Among all patients, 113 patients (61%) received EPO. Twenty-six patients on study A and 7 patients on study B developed a VTE. Treatment with EPO was not associated with a higher rate of VTE compared to no treatment with EPO (19% versus 22%, Fisher exact test, p=0.8). The mean peak hemoglobin for patients with a VTE was not statistically different from patients without a VTE (14.2 vs. 13.8 g/dL, p=0.3). Similarly, the mean on study hemoglobin was not different among patients with a VTE and those without a VTE (11.7 vs. 11.6 g/dL, p=0.8). The mean hemoglobin at the time of the VTE was 12.0 g/dL (S.D. 1.5g/dL).

Conclusion: Our results do not indicate an association between EPO and VTE in MM patients receiving anthracycline-based chemotherapy with an immunomodulator and aspirin prophylaxis. Uncontrolled erythrocytosis does not appear to be associated with VTE in this patient population. Of note, target hemoglobins were not commonly exceeded. Low dose Aspirin (81mg) is an effective prophylaxis for VTE in multiple myeloma patients receiving anthracycline based therapy with thalidomide or lenalidomide in conjunction with the use of erythropoietin therapy.